The Program in Radiation Biology is focused on ways in which the effectiveness of radiotherapy can increase local tumor control and survival of cancer patients. Three different approaches are being pursued to achieve this goal: 1) Develop pharmacologic and biologic agents to combine with radiotherapy and chemotherapy to improve local tumor control and prevent metastatic spread; 2) Design new approaches to administer radiotherapy or combined modality therapy to test in clinical trials; 3) Identify genetic determinants using yeast and mammalian genetics that influence the response of tumors to radiation or the combination of chemotherapy and radiation. The research of program members has resulted in a series of important findings that include the identification of Prl-3 (phosphatase of regenerating liver-3) as a p53 target gene, the identification of the molecular pathways that give rise to intercellular polarity, developing new hypoxic-specific cytotoxins for cancer therapy, identifying new genes that are essential for adaptation to stress that are essential for metastasis, elucidating the signaling pathways that integrate DNA damage recognition, checkpoint signaling and DNA repair, generation of mouse models to study in vivo stress responses and targeted therapy, expanding the use of hypofractionated radiosurgery to treat solid tumors, developing new approaches to generate protons for therapeutic use and developing molecular and functional imaging techniques to direct the delivery of radiotherapy. The 26 program members representing the School of Medicine and the School of Humanities and Sciences are supported by peer-reviewed research and training grants totaling $6,826,435, including 16 R01s, 2P01s, 2 T32s. The members of this program are highly motivated and interactive in their goal to take fundamental discoveries in the laboratory and develop them to increase the efficacy of radiotherapy to control tumor growth and metastasis.